NCT03050801

Functional Connectivity as a Biomarker of rTMS

Completed Phase 1, PHASE2 Results posted Last updated 12 April 2021

What this trial tests

Phase 1, PHASE2 trial testing rTMS in Traumatic Brain Injury in 68 participants. Completed in 7 August 2020.

Timeline

24 March 2017

Primary endpoint
10 March 2020

7 August 2020

Quick facts

Lead sponsor	National Institute of Neurological Disorders and Stroke (NINDS)
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	68
Start date	24 March 2017
Primary completion	10 March 2020
Estimated completion	7 August 2020
Sites	1 location across United States

Drugs / interventions tested

• rTMS

Conditions studied

• Traumatic Brain Injury — all drugs for Traumatic Brain Injury →

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Who can join

Adults 18 to 50, any sex, with Traumatic Brain Injury. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Functional Connectivity (FC) Changes Between the Left Hippocampus and Left Parietal Cortex Primary · Changes are calculated before and the day after rTMS

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at sufficient intensity to trigger action potentials in nearby neurons.The motor threshold is defined as the minimum percentage of the stimulator output to elicit a motor evoked potential. Repetitive TMS (rTMS) was delivered at 100% of the motor evoked potential threshold with repeated magnetic pulses at a frequency of 20 Hz. Functional MRI (fMRI) measures the change in oxygenated blood in the bra

Group	Value	95% CI
Experiment 1: Parietal Cortex rTMS Stimulation - 1 Day	-0.03	± 0.089
Experiment 1: Parietal Cortex rTMS Stimulation - 3 Days	0.13	± 0.202
Experiment 1: Parietal Cortex rTMS Stimulation - 4 Days	0.02	± 0.123
Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days	-0.01	± 0.109
Experiment 2: Vertex rTMS Stimulation - 3 Days	-0.05	± 0.141
Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days	0.03	± 0.088

Associative Memory Test Score Changes Primary · Changes are calculated before and the day after rTMS and before and 7-14 days after rTMS

Participants studied 20 face-word pairs, and after a short delay, were required to recall the word associated with each pair. The number of correctly remembered pairs was recorded. rTMS was administered over different regions of the brain over 3 days. The Associative Memory test was administered at baseline (within a week before the first rTMS session), 1 day after the last rTMS session, and again 7-14 days after the last rTMS session. We calculated improvements on this task by subtracting the number of successfully remembered pairs 1 day after stimulation from the number remembered at baselin

Changes one day after rTMS

Group	Value	95% CI
Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days	0.08	± 0.133
Experiment 2: Vertex rTMS Stimulation - 3 Days	0.01	± 0.166
Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days	0.03	± 0.035

Changes 7-14 days after rTMS

Group	Value	95% CI
Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days	0.08	± 0.173
Experiment 2: Vertex rTMS Stimulation - 3 Days	0.02	± 0.149
Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days	0.13	± 0.071

Implicit Weather Prediction Task (WPT) Secondary · Changes are calculated before and the day after rTMS, and before and 7-14 days after rTMS

Participants learn implicit, probabilistic relationships between stimuli and responses through feedback. 1, 2 and 3 card combinations of 4 possible cards are presented on a computer; the subject is asked to predict whether it will be rainy or fine. After each prediction, the subject receives corrective feedback. Each card is independently associated with one outcome with a fixed probability.The WPT was administered at baseline and 1 day after and 7-14 days after the last rTMS session. Scores at each time point represent the proportion of responses associated with a reward (optimal responses).

Changes one day after rTMS

Group	Value	95% CI
Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days	-0.03	± 0.158
Experiment 2: Vertex rTMS Stimulation - 3 Days	0.06	± 0.196
Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days	0.06	± 0.02

Changes 7-14 days after rTMS

Group	Value	95% CI
Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days	-0.02	± 0.143
Experiment 2: Vertex rTMS Stimulation - 3 Days	0.02	± 0.156
Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days	0.01	± 0.03

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected during and immediately after study procedures. Participants experiencing adverse events at completion of study procedures, were followed until AE resolution.. Reporting threshold: 4.4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experiment 1: Parietal Cortex rTMS Stimulation - 1 Day

Serious: 0/3 (0%)

Deaths: 0/3

Experiment 1: Parietal Cortex rTMS Stimulation - 3 Days

Serious: 0/13 (0%)

Deaths: 0/13

Experiment 1: Parietal Cortex rTMS Stimulation - 4 Days

Serious: 0/8 (0%)

Deaths: 0/8

Experiment 2: Parietal Cortex rTMS Stimulation - 3 Days

Serious: 0/21 (0%)

Deaths: 0/21

Experiment 2: Vertex rTMS Stimulation - 3 Days

Serious: 0/19 (0%)

Deaths: 0/19

Experiment 2: Prefrontal Cortex rTMS Stimulation - 3 Days

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (2 terms — click to expand)

Reaction	System	Experiment 1: Parietal Cor…	Experiment 1: Parietal Cor…	Experiment 1: Parietal Cor…	Experiment 2: Parietal Cor…	Experiment 2: Vertex rTMS …	Experiment 2: Prefrontal C…
Intolerance to stimulation	Nervous system disorders	—	—	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—	—	—

Data from ClinicalTrials.gov NCT03050801 adverse events section.

Sponsor's own description

Background:

Traumatic brain injury (TBI) damages the connections between brain cells. This can lead to problems like memory loss. Repetitive transcranial magnetic stimulation (rTMS) can help improve connections between brain areas in healthy people. Researchers want to see if it can be useful in patients with memory problems after TBI.

Objective:

To see how repetitive transcranial magnetic stimulation can be used to improve the connections between parts of the brain and whether this will lead to changes in memory.

Eligibility:

Adults 18-50 years old with TBI who can speak and write in English.

Healthy volunteers the same age and English ability.

Design:

Participants will be screened with a neurological exam and may have a urine pregnancy test.

Participants with TBI will have 7-15 visits. Healthy volunteers will have 2-8 visits.

At the visits, participants will have all or some of the following:

* MRI for about 1 hour. Participants will lie in a machine that takes pictures in a magnetic field. Participants will do some memory tasks.
* Memory and attention tasks with pictures and with a computer
* Questions about their mental state and well-being
* TMS: A wire coil is held on the scalp and a short electrical current passes through it. Participants will hear a click and feel a pulling or twitch. They may be asked to make simple movements. rTMS is repeated magnetic pulses in short bursts. They will have this for about 20 minutes.

A week after the last visit, some participants will return for a memory test.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.